P535: OUTCOMES OF INVESTIGATIONAL AGENTS VS STANDARD THERAPIES IN AML AT SALVAGE 2 AND BEYOND
Authors: Daniel Nguyen, Hagop Kantarjian, Aram Bidikian, Courtney Dinardo, Tapan Kadia, Naval Daver, Gautam Borthakur, Elias Jabbour, Musa Yilmaz, Nicholas Short, Abhishek Maiti, Koji Sasaki, Guillermo Montalban-Bravo, Danielle Hammond, Sherry Pierce, Michael Andreeff, Guillermo Garcia-Manero, Farhad Ravandi, Ghayas Issa
Journal: HemaSphere (2023)

Background: The treatment arsenal of acute myeloid leukemia (AML) has expanded over the past decade, with multiple agents receiving regulatory approval, thus providing new tools to individualize AML therapy. However, patients (pts) with relapsed or refractory (R/R) disease continue to have dismal outcomes. Pts and clinicians often must decide between standard salvage treatment regimens or enrollment into clinical trials. Aims: The purpose of our study was to compare outcomes of standard salvage regimens vs investigational agents given at salvage 2 and beyond to guide clinical decision making. Methods: We conducted a retrospective analysis of pts treated at MD Anderson between 2012 and 2020 with R/R AML who received either investigational agents or standard treatment regimens at salvage 2 and beyond. Salvage lines were defined whenever treatment was given for refractory or relapsed disease. Investigational agents were those non-FDA approved and consisted of chemotherapeutic, targeted, or immunotherapy agents given as single agents or in combination. Therapies that would eventually become FDA-approved were included in the investigational group if given before FDA approval. Standard salvage included both high-intensity and low-intensity regimens. Results: We screened 590 adult pts with R/R AML who received either investigational or standard salvage 2 therapy. The median age was 66 (range 17-87) and 63 (range 17-85) in the investigational and standard salvage cohorts, respectively (P=0.0008). There were 354 pts (60%) who received an investigational agent at salvage 2 vs 236 pts (40%) who received standard salvage chemotherapy (Table 1). At salvage 2, standard regimens achieved higher rates of complete remission (CR) and complete remission with incomplete count recovery (CR/CRi) compared to investigational agents (27% vs 12%, P=0.0001). There was no difference in the number of pts who were able to undergo transplant consolidation (11% vs 7%, P=0.11). The 30-day and 60-day mortality were significantly higher in the standard salvage cohort compared to the investigational cohort, with rates of 12% (27/236 pts) and 17% (41/236 pts) vs 5% (19/354 pts) and 7% (27/354 pts), respectively (P=0.003, P=0.0004). Importantly, there was no difference in OS (median: 3.8 vs 4.5 months, P=0.76) or EFS (median: 1.4 vs 2.2 months, P=0.66) between standard and investigational therapies respectively. A subgroup analysis of the standard therapy cohort comparing standard regimens with or without venetoclax revealed that standard therapies incorporating venetoclax resulted in a statistically significant but marginal increase in EFS (median: 1.8 months vs 1.3 months, P=0.03), and no difference in OS (median: 4.5 months vs 3.6 months, P=0.24). We subsequently examined the response rates for lines of therapy given at salvage 3 and beyond, of which there were 591 investigational lines and 308 standard salvage lines. We found higher rates of CR/CRi in the standard salvage regimens compared to investigational agents (13% vs 5%, P=0.0001), but continued to find that standard salvage was associated with higher rates of 30-day mortality (15% vs 7%, P=0.0005), and 60-day mortality (20% vs 11%, P=0.0007). Summary/Conclusion Marginally higher remission rates achieved by standard regimens given at salvage 2 and beyond compared with investigational agents did not translate to a survival benefit with higher rates of early mortality. Therapeutic outcomes of R/R AML remain disappointing. We show that enrollment of pts with R/R AML into clinical trials is a suitable alternative to standard salvage regimens, as it is in the best interest of pts while also serving as the engine of discovery for new therapies aimed at improving these dismal outcomes.Keywords: AML